Cervical cancer is the second leading cause of death for women worldwide with 85% of deaths occurring in low- and middle-income countries (LMICs), despite the fact that well-established interventions exist for pre- invasive disease. One of the barriers to cervical cancer prevention is reliable access to treatment. Cryotherapy, which is the current therapy recommended by the World Health Organization (WHO) for treating cervical pre- cancer in LMICs, requires a continuous supply of pressurized liquid nitrogen, which is expensive and difficult to transport, and does not adequately treat advanced lesions. More recently, the thermocoagulator has gained acceptance for ablation of cervical pre-cancer lesions because of its ability to treat both low-grade and high- grade pre-cancers. However, thermocoagulation (while effective) has a price point of $1500 to $3,000, which is inaccessible at the community level. These well-documented shortcomings demonstrate a clear unmet clinical need to develop new treatment strategies to prevent cervical cancer in LMICs. To meet this unmet need, our group has recently developed a novel tumor ablation technique based on ethanol ablation. Ethanol ablation was previously developed as a low-cost treatment for encapsulated, inoperable liver tumors, and involves manual injection of pure ethanol into malignant tissue. Preclinical studies showed that while manual injection of pure ethanol is ineffective in treating epithelial lesions, a novel formulation that combines ethanol with an agent ethyl cellulose substantially improved efficacy and induced complete regression of 7 out of 7 tumors. Ethyl cellulose not only makes ethanol more viscous (which prevents backflow) but also forms a gel in an aqueous medium, which sequesters ethanol in the region of interest. Gel ethanol does not require hard-to-supply consumables and has the potential to be ultra-low-cost and highly portable. The goal of this proposal is to optimize the injection procedure and delivery mechanism to treat pre-invasive lesions of the cervix as an alternative to thermocoagulation. To achieve this, the aims are to: 1) establish a method to optimize gel ethanol delivery, 2) assess the safety and efficacy of optimized delivery in a large animal model, and 3) conduct an initial assessment of an optimized delivery procedure in the human cervix. The K99 phase includes the optimization of the gel ethanol injection procedure in Aim 1 and the preclinical studies proposed in Aim 2, which will lay the groundwork for a pre-investigational new drug (IND) meeting and transitioning to clinical studies. The R00 phase includes the optimization of a gel ethanol delivery mechanism and translation to human studies. An independent clinical study is proposed for the R00 portion of the award. These aims will lead to an optimized gel ethanol delivery procedure whose safety and efficacy are validated in a large animal model with an initial assessment in human cervices, which will lay the groundwork for clinical translation.